Objectives. Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods. We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results. Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion. The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023

Aims. Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. Methods. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation. Results. All rats tolerated the treatment well and no obvious adverse effects were found. By comparison, the HSR signal (three hrs/day) treatment group achieved the best healing outcome, in that endochondral ossification and bone consolidation were enhanced. In addition, HSR signal treatment (one one hr/day) had similar effects to treatment using the classic signal (three three hrs/day), indicating that treatment duration could be significantly shortened with the HSR signal. Conclusion. HSR signal may significantly enhance bone formation and shorten daily treatment duration in DO, making it a potential candidate for a new clinical protocol for patients undergoing DO treatments. Cite this article: Bone Joint Res 2021;10(12):767–779

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327

Aim. Bone infections often manifest with soft tissue complications such as severe scarring, fistulas, or ulcerations. Ideally, their management involves thorough debridement of infected bone and associated soft tissues, along with achieving stable bone structure, substantial tissue coverage, and long-term antibiotic therapy. The formation of a multidisciplinary team comprising orthopedic surgeons, plastic surgeons, and infectious disease specialists is essential in addressing the most complex cases. Method. We conducted a retrospective study during six years (2018-2023) at our university center. Focusing on the most challenging cases, we included patients with bone infections in the leg and/or foot requiring free flap reconstruction. Each patient underwent simultaneous bone debridement and reconstruction by the orthopedic team, alongside soft tissue debridement and free flap reconstruction by the plastic surgery team. Targeted antibiotic therapy for either 6 weeks (acute) or 12 weeks (chronic osteitis) was initiated based on intraoperative cultures. Additional procedures such as allografts, arthrodesis, or autografts were performed if necessary. We analyzed the rates of bone union, infection resolution, and limb preservation. Results. Forty-five patients were enrolled. Twenty-four patients (53.3%) had urgent indications (e.g., open infected fractures, osteitis, acute osteoarthritis, or wound dehiscence), while 21 (46.7%) underwent elective surgery (e.g., septic pseudarthrosis or chronic osteitis). Two patients underwent amputation due to flap failure (4.4%), and one patient was lost to follow-up. Follow-up of the remaining 42 patients averaged 28 months (range: 6–60 months). During this period, 35 patients (83.4%) experienced no recurrence of infection. Similarly, 35 patients (83.4%) achieved bone union. Overall, the rate of lower limb preservation was 93.3%. Conclusions. Managing bone infection coupled with soft tissue defects brings significant challenges. Although the majority of patients treated here belong to a complex framework based on the BACH classification, the outcomes achieved here appear to align with those of the simpler cases, thanks to optimal care with a dedicated septic ortho-plastic team. Our study demonstrates a notable success rate in treating infection, achieving bone consolidation, and preserving lower limb function

Aim. Treatment of infected and non-infected non-unions remain a major challenge after orthopedic fracture-related surgery. In clinical practice, several revision surgeries are usually required, including a radical debridement and exchange of implants, to control or even eradicate the infection to finally achieve bone healing. However, a clear treatment algorithm in clinical practice may be difficult to follow due to the heterogeneous patient population. Thus, so controlled settings for research purposes is better achieved in standardized animal studies. So far, there exists no multi-stage animal model that can be realistically transferred to the clinical situation in humans. The importance of such a model is obvious in order to be able to investigate different therapy concepts for infected and non-infected non unions. Methods. In 20 female Sprague-Dawley rats, a critical size defect by a femur osteotomy with 5 mm width was done. The periosteum at the fracture zone was cauterized proximal and distal to the osteotomy to achieve an hypovascularized situation. After randomization, 10 animals were intramedullary infected with a multisensible Staph. aureus strain (10. 3. CFU). After 5 weeks, a second surgery was performed with removing the K-wire, debridement of the osteotomy-gap and re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, by the score of Lane and Sandhu and to quantify callus formation and the mineralized area of the callus. Results. 5 weeks after the first surgery a non-union had formed in all septic and aseptic animals. According to the Lane and Sandhu score a significantly higher callus formation was found in the infected group. In all infected animals, the inoculated Staph. aureus strain was detected during the revision surgery. 8 weeks after the second surgery no bone healing could be detected in the µ-CT analysis in both groups and biomechanical testing showed a significant lower maximum torque in both groups as compared to the untreated contralateral femura. Conclusion. Here we show first results of a new two-stage pseudarthrosis animal model, which reflects a very realistic clinical situation of an infection-related non-union model. Based on this model, various therapeutic strategies in the treatment of infectious and non-infectious pseudarthrosis, such as the use of bone substitutes, can be evaluated in further studies

Distraction histogenesis (DH) techniques have been widely accepted and practiced in orthopaedics, traumatology, and craniofacial surgery over the last two decades. Using DH methods, many previously untreatable conditions have been successfully managed with outstanding clinical outcomes. The biological mechanisms underlying DH have been studied and the tension-stress principles of tissue regeneration are attributed to upregulated gene expression, enhanced cell proliferation, angiogenesis and tissue remodelling and endogenous stem cell mobilization. The new methods of enhancing bone consolidation in DH are proposed and need further clinical studies. The novel applications of DH have now been extended for the treatment of vascular diseases, cranial defect (with neuronal disorders), hip and spinal deformity corrections and soft-tissue defects in addition to various bone defects and deformities. There are more surprises and novel mechanisms yet to be discovered for these novel applications of DH

Introduction: The aim of this study was to evaluate direct mechanical measurements from an external fixator as an alternative method to DEXA to examine the healing progress of patients undergoing distraction osteogenesis (DO). Methods: Five patients were evaluated concurrently by BMD estimates and direct mechanical measurements from an external fixator to examine bone consolidation approximately every six weeks after the end of distraction. For mechanical measurements, all rods were removed from the external fixator and replaced with three load cells. An axial load of 10 kg was applied to the tibia and the load recorded from the three load cells was used to calculate the proportion of the load supported by the fixator (Load Share Ratio, LSR), which indicates the stiffness of the newly developed bone. Results: The LSR decreased significantly for all patients (r2=0.63, p < 0.01), indicating increased bone stiffness. DEXA based BMD estimates decreased for two of five patients despite normal healing progress and likewise BMD and LSR were weakly correlated (r2=0.22, p > 0.05). Discussion: Bone consolidation is often accompanied by changes in bone geometry, which can make DEXA based BMD estimates inaccurate for this application. Mechanical measurements from external fixators are not subject to this error and therefore could be a more reliable method to evaluate the healing progress of patients undergoing DO. Conclusion: Direct mechanical measurements from an external fixator may be an alternative procedure to improve the evaluation of healing progress during DO

Segmental bone transport (SBT) with an external fixator has become a standard method for treatment of large bone defect. However, a long time-application of devices can be very troublesome and complications such as nonunion is sometimes seen at docking site. Although there have been several studies on SBT with large animal models, they were unsuitable for conducting drug application to improve SBT. The purpose of this study was to establish a bone transport model in mice. Six-month-old C57BL/6J mice were divided randomly into bone transport group (group BT) and an immobile control group (group EF). In each group, a 2-mm bone defect was created in the right femur. Group BT was reconstructed by SBT with external fixator (MouseExFix segment transport, RISystem, Switzerland) and group EF was fixed simply with unilateral external fixator (MouseExFix simple). In group BT, a bone segment was transported by 0.2 mm per day. Radiological and histological studies were conducted at 3 and 8 weeks after the surgery. In group BT, radiological data showed regenerative new bone consolidation at 8 weeks after the surgery, whereas high rate of nonunion was observed at the docking site. Histological data showed intramembranous and endochondral ossification. Group EF showed no bone union. In this study, experimental group showed good regenerative new bone formation and was similar ossification pattern to previous large animal models. Thus, the utilization of this bone defect mice model allows to design future studies with standardized mechanical conditions for analyzing mechanisms of bone regeneration induced by SBT

Aims

Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI.

Introduction. Since 2005, we have performed implantation of bone marrow-derived mononuclear cells for osteonecrosis of the femoral head in order to improve vascularization and bone repair. This study focused on early bone repair of osteonecrosis of the femoral head after transplantation of bone marrow-derived mononuclear cells (BMMNC). Patients and Methods. Twenty-two patients (30 joints) who had bilateral osteonecrosis followed for more than 2 years after BMMNC implantation were evaluated. Eight women and 14 men were included. Their mean age at surgery was 41 years (range, 18 to 64 years) and the mean follow-up period was 31 months. Pre-operative stage according to the ARCO classification was Stage 2 in 25 joints and Stage 3 in 5 joints. The mean volume ratio of osteonecrosis was 21%. For preparing BMMNC, about 700ml of bone marrow was aspirated from the ilium and centrifuged using a Spectra cell separator (Gambro). The BMMNC were seeded to interconnected porous calcium hydroxyapatite (IP-CHA) and implanted to the osteonecrotic lesion. As a control, cell-free IP-CHA was implanted for 8 patients (9 joints). A woman and 7 men were included. The mean age at surgery was 49 years (range, 28 to 73 years) and the mean follow-up period was 37 months. Preoperative stage was stage 2 in all patients. The mean volume ratio of osteonecrosis was 22%. At post-operative evaluations; progression of collapse, consolidation at reactive zone, post-operative course of volume rate of osteonecrosis, and bone absorption at osteonecrosis was assessed. Results. Shrinkage of osteonecrosis has been observed subsequent to bone consolidation at the transitional zone which progressed from 3 to 6 months post-operatively in the BMMNC-seeded group. Progression of collapse more than 2 mm was detected in 4 joints (13%), and hip arthroplasty was performed in 1 joint (3%). Consolidation at the reactive zone was detected in 28 joints (93%) and the volume rate of osteonecrosis significantly decreased by 12 months after surgery. Bone resorption at the osteonecrotic lesion was observed in 14 joints (47%). Meanwhile, subtle bone consolidation was detected after 12 months post-operatively in the control group. Progression of collapse was observed in 6 joints (67%) and further surgical treatments were needed in 3 joints (33%). Conclusion. This study found that BMMNC was beneficial to osteonecrosis of the femoral head from the viewpoint of prevention of collapse

The thrombin-related peptide, TP508, a synthetic 23 amino acid peptide, has been shown to promote soft tissue, cartilage and fracture repair. We have previously demonstrated that two injections of TP508 have signifi-cantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to test if a single injection of TP508 in a slow-releasing preparation will have the similar effects. Unilateral tibial osteoectomies were stabilized with M100 Orthofix lengtheners in 17 male adult NZW rabbits. After 7 days, lengthening was initiated at a rate of 1.4 mm/day for 6 days. The following treatments were given: Group 1: TP508 in saline (300ug/300ul, n=6) was injected into the osteotomy gap at day of surgery and into the lengthening gap at end of lengthening. Group 2 (Control): Dextran gel (300ul, n=6) and Group 3: 300ul Dextran gel mixed with microspheres containing 300ug TP508 (n=5), was injected into the lengthening gap at end of lengthening. All animals were terminated 2 weeks after lengthening. Bone formation was assessed by weekly radiography and the specimens were subject to pQCT, microCT and histology examinations. On radiographies there was more bone formation in the TP508 treated groups than that of the control group at 1st week post-lengthening and complete union was seen in 50% rabbits in Group 1, 33% in Group 2, and 60% in Group 3 at termination. The mean BMD of the regenerates was significantly higher in the TP508 treated groups than that of the control group (p< 0.05). MicroCT analysis demonstrated advanced bone formation in the TP508 treated animals. For histology, the regenerates were mainly consisted of woven bone of neocortilization and callus remodelling in Groups 1 and 3, whereas in Group 2, focal defects with cartilaginous tissues were frequently seen. In conclusion we have demonstrated that a single injection of TP508 in the form of slow releasing micro-spheres has enhanced bone consolidation during distraction osteogenesis. TP508 may therefore be applied in the slow-releasing preparation for augmenting bone formation at reduced doses, costs and risks of infections through repeated injections

Background. Despite the known multifactorial nature of scaphoid wrist fracture non-union, a possible genetic predisposition for the development of this complication remains unknown. This pilot study aimed to address this issue by performing Single Nucleotide Polymorphisms (SNPs) analysis of specific genes known to regulate fracture healing. Materials and Methods. We reviewed 120 patients in a retrospective case-control study from the Hand Surgery Department of Asepeyo Hospital. The case group comprised 60 patients with confirmed scaphoid wrist non-union, diagnosed by Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). The control group comprised 60 patients with scaphoid fracture and complete bone consolidation. Sampling was carried out with a puncture of a finger pad using a sterile, single-use lancet. SNPs were determined by real-time polymerase chain reaction (PCR) using specific, unique probes with the analysis of the melting temperature of hybrids. The X2 test compared genotypes between groups. Multivariate logistic regression analysed the significance of many covariates and the incidence of scaphoid wrist non-union. Results. We found significant differences in subjects who had a smoking habit (p=0.001), high blood pressure (p<0.001), and surgical treatment (p=0.002) in patients with scaphoid non-union. There were more Caucasians (p=0.04) and males (p=0.001) in the case group. Falls were the main mechanism of fracture. The CC genotype in GDF5 (rs143383) was more frequent in patients with scaphoid non-union compared to the controls (p=0.02). CT was prevalent in the controls (p=0.02). T allele in GDF5 was more frequent in patients without non-union (p=0.001). Conclusions. Individuals who were carriers of the CC genotype in GDF5 showed higher susceptibility to suffering scaphoid wrist non-union. Furthermore, being a carrier of CT and T allele suggests that this could be behave as a protection factor against non-union. This is the first clinical study to investigate the potential existence of genetic susceptibility to scaphoid wrist fracture non-union. Level of evidence. Level III, Cross Sectional Study, Epidemiology Study

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.

The February 2023 Trauma Roundup³⁶⁰ looks at: Masquelet versus bone transport in infected nonunion of tibia; Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multicentre randomized clinical trial; Is the T-shaped acetabular fracture really a “T”?; What causes cut-out of proximal femur nail anti-rotation device in intertrochanteric fractures?; Is the common femoral artery at risk with percutaneous fragility pelvis fixation?; Anterior pelvic ring pattern predicts displacement in lateral compression fractures; Differences in age-related characteristics among elderly patients with hip fractures.

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Background. Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. Within the REBORNE project, a multi-center orthopaedic clinical trial was focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union. Methods. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-ups (6, 12 and 24 weeks post-surgery). Results. A significant relationship with age was found only at Visit 6, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the starting value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with negative outcome. The BTM profile indicated remarkable bone formation activity after 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome. Conclusion. BTM related to bone cell function are useful to measure the efficacy of a regenerative approach based on expanded MSC. Level of evidence. Diagnostic Level IV. Work supported by the EC, Seventh Framework Programme (FP7), through the REBORNE Project, grant agreement no. 241879

Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. The REBORNE project entailed a multi-center orthopaedic clinical trial focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial, to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union. Peripheral blood was collected from patients at fixed time-endpoints, that is at 6,12 and 24 weeks post-surgery for implantation of expanded autologus MSC and bone-like particles. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-up visits. A significant relationship with age was found only at 6 months, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the baseline value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with a negative outcome. The BTM profile apparently indicated a remarkable bone formation activity 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome. Blood markers related to bone cell function are useful to measure the efficacy of a expanded MSC-regenerative approach applied to long bone non-unions. Changes of the markers may provide a support to radiological assessment of bone healing

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Autologous bone grafting for bone defect reconstruction is associated with complications including donor site morbidity, infection risk, pain and surgical time. Therefore, bone graft substitutes provide an alternative for distinct indications and different characteristics with regard to their mechanical properties and resorption rates. In order to fill the loss of bone substance and to control the infection, we tried the efficacy of Cerament™G, a new absorbable composite of Calcium Sulphate and Hydroxyapatite with Gentamicin. We present 3 male patients aged between 45 and 68 years affected by post-traumatic severe septic non union of femur, tibia and foot. The first patient with femur fracture was involved in a car accident (mixed flora Acinetobacter Baumanii, MRSA and Klebsiella pneumoniae carbapenemase (KPC)-producing), the second patient with femur and foot fracture falled by height in a work accident (MRSA) and the third one had a chronic tibial osteomyelitis several years after a road accident (Pseudomonas Aeruginosa). All 3 patients had undergone previous surgery. The first patient had several operations including multiple bone resection and debridement with external fixator, occlusion of superficial femoral artery with arterial bypass and finally debridement with implantation of Cerament™ G with external fixator and long term antibiotic therapy. The other 2 patients were subjected to resection of tissue septic with debridement, implantation of Cerament™ G and soft tissue closure and systemic antibiotics. Clinical and radiographic outcome were assessed at final follow-up (mean 8 months; range 8–18). The follow-up was 8–18 months with examining clinical, radiographic, CT scan and laboratory tests. The patients had self-limiting fluid leakage. There was no recurrence of infection during the follow-up period. Bone ingrowth occurred in all cases with limb shortening. Cerament™ G gives good elution of antibiotic and allows bone ingrowth. The implantation of Cerament™ G was associated with good clinical outcomes and satisfactory bone consolidation. We acknowledge Antonella Esposito for septic nursing assistance